{"id":"ctdna-tests","name":"ctDNA tests roadmap: from a curiosity in plasma to blood tests that decide treatment","route":"/roadmaps/ctdna-tests/","eras":[{"era":"1948-1994","title":"A curiosity in plasma","description":"Mandel and Metais reported nucleic acids in human blood plasma in 1948, and in 1977 Leon and colleagues found that people with cancer carried more free DNA in their serum and that levels fell when treatment worked. Nobody could yet say which fragments came from the tumour, so for four decades this stayed an observation rather than a test.","status":"historic","refs":[{"id":"cfdna","kind":"term","name":"Cell-free DNA (cfDNA)","route":"/terms/cfdna/","tldr":"Short pieces of DNA floating in the blood, shed by dying cells all over the body. Most is from normal cells; the small tumour-derived fraction (ctDNA) is what liquid biopsies fish out."},{"id":"ctdna","kind":"term","name":"Circulating tumour DNA (ctDNA)","route":"/terms/ctdna/","tldr":"Circulating tumour DNA (ctDNA) consists of fragments of DNA shed by tumour cells into the blood, detectable with sensitive sequencing."},{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/","status":"standard-of-care","tldr":"A blood test that reads fragments of DNA shed by the tumour, so you can genotype or monitor cancer without a needle in the tumour."},{"id":"klaus-pantel","kind":"person","name":"Klaus Pantel","route":"/people/klaus-pantel/","tldr":"Klaus Pantel is a pioneer of circulating tumour cell research and the liquid biopsy field."}],"trials":[],"papers":[]},{"era":"2008-2016","title":"Proof that blood tracks the tumour","description":"Digital PCR and deep sequencing made it possible to count tumour-specific mutations in plasma: Diehl and colleagues showed mutant DNA rising and falling with disease in 2008, Dawson and colleagues tracked metastatic breast cancer with it in 2013, and Bettegowda and colleagues detected ctDNA across early- and late-stage cancers in 2014. Tie and colleagues then showed in 2016 that ctDNA found after surgery for stage II colon cancer predicted recurrence, the observation the residual disease trials were built on.","status":"historic","refs":[{"id":"ctdna","kind":"term","name":"Circulating tumour DNA (ctDNA)","route":"/terms/ctdna/","tldr":"Circulating tumour DNA (ctDNA) consists of fragments of DNA shed by tumour cells into the blood, detectable with sensitive sequencing."},{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/","status":"standard-of-care","tldr":"A blood test that reads fragments of DNA shed by the tumour, so you can genotype or monitor cancer without a needle in the tumour."},{"id":"nitzan-rosenfeld","kind":"person","name":"Nitzan Rosenfeld","route":"/people/nitzan-rosenfeld/","tldr":"Showed that whole-exome sequencing of blood can track how a cancer evolves, and co-founded Inivata."},{"id":"dawson-sarah-jane","kind":"person","name":"Sarah-Jane Dawson","route":"/people/dawson-sarah-jane/","tldr":"A ctDNA pioneer whose early work showed blood could track breast cancer better than protein markers or imaging."},{"id":"nickolas-papadopoulos","kind":"person","name":"Nickolas Papadopoulos","route":"/people/nickolas-papadopoulos/","tldr":"Co-developed CancerSEEK, the blood test that showed multi-cancer early detection is possible, and ran the first prospective screening study of it."},{"id":"alberto-bardelli","kind":"person","name":"Alberto Bardelli","route":"/people/alberto-bardelli/","tldr":"Used ctDNA to show how colorectal cancers evolve resistance to EGFR antibodies and how that resistance can fade."},{"id":"jeanne-tie","kind":"person","name":"Jeanne Tie","route":"/people/jeanne-tie/","tldr":"Led DYNAMIC, the first randomised trial to show ctDNA can safely guide who needs chemotherapy after colon cancer surgery."},{"id":"clonal-evolution","kind":"pathway","name":"Clonal evolution & minimal residual disease","route":"/pathways/clonal-evolution/","tldr":"A tumour is a population that evolves by natural selection. Treatment kills the sensitive cells and selects the rest, which is why resistance is the rule; measuring the surviving population (MRD) and adapting therapy is the counter-strategy."}],"trials":[],"papers":[]},{"era":"2016-2020","title":"Regulators accept a blood genotype","description":"On 1 June 2016 the FDA approved the cobas EGFR Mutation Test v2 for plasma, the first liquid biopsy companion diagnostic, letting lung cancer patients start erlotinib on a blood result when tissue was unavailable. Two broad panels followed in August 2020: Guardant360 CDx on 7 August and FoundationOne Liquid CDx on 26 August, each a companion diagnostic for several drugs, with a negative blood result sent back to tissue testing.","status":"historic","refs":[{"id":"cobas-egfr-mutation-test","kind":"drug","name":"cobas EGFR Mutation Test v2","route":"/drugs/cobas-egfr-mutation-test/","status":"approved","tldr":"The lung cancer gene test that became the first blood-based companion diagnostic the FDA ever approved."},{"id":"guardant360-cdx","kind":"drug","name":"Guardant360 CDx","route":"/drugs/guardant360-cdx/","status":"approved","tldr":"A blood test that reads a tumour's mutations without a tissue biopsy and is the FDA-approved gateway to several targeted drugs."},{"id":"foundationone-cdx","kind":"drug","name":"FoundationOne CDx / Liquid CDx","route":"/drugs/foundationone-cdx/","status":"approved","tldr":"The FDA-approved tissue (324 genes) and blood genomic tests that serve as companion diagnostics for dozens of drugs."},{"id":"companion-diagnostic","kind":"technology","name":"Companion diagnostics","route":"/technologies/companion-diagnostic/","status":"standard-of-care","tldr":"The test that decides whether a specific drug is right for you, approved together with the drug."},{"id":"roche-genentech","kind":"company","name":"Roche / Genentech","route":"/companies/roche-genentech/","tldr":"Creator of Herceptin, Avastin, and Rituxan, and owner of Foundation Medicine; the company that defined antibody oncology."},{"id":"guardant-health","kind":"company","name":"Guardant Health","route":"/companies/guardant-health/","tldr":"Liquid biopsy leader: Guardant360 for genotyping, Reveal for MRD, Shield for screening."},{"id":"foundation-medicine","kind":"company","name":"Foundation Medicine (Roche)","route":"/companies/foundation-medicine/","tldr":"Maker of the FDA-approved FoundationOne CDx genomic test used across dozens of drug labels."},{"id":"erlotinib","kind":"drug","name":"Erlotinib","route":"/drugs/erlotinib/","status":"approved","tldr":"Erlotinib was one of the first EGFR pills for lung cancer; it was approved before anyone knew EGFR mutations predicted who would respond, then redefined by them."},{"id":"osimertinib","kind":"drug","name":"Osimertinib","route":"/drugs/osimertinib/","status":"approved","tldr":"Osimertinib (Tagrisso) is the standard pill for EGFR-mutant lung cancer, now also given after surgery and with chemotherapy or after chemoradiation."}],"trials":[],"papers":[]},{"era":"2019-2021","title":"Tumour-informed residual disease tests reach the clinic and the payer","description":"Signatera sequences each patient's tumour, picks 16 mutations, and looks for them in plasma after surgery; in the GALAXY registry a positive test four weeks after colorectal surgery carried a tenfold higher recurrence risk. Medicare's MolDX programme finalised coverage for serial Signatera testing in stage II and III colorectal cancer on 3 September 2020, and its coverage article for residual disease tests now lists several tests and cancers, which is how tumour-informed testing became routine before any randomised trial had finished.","status":"current","refs":[{"id":"signatera","kind":"drug","name":"Signatera","route":"/drugs/signatera/","status":"established","tldr":"Signatera is Natera's tumour-informed blood test that tracks 16 mutations from each patient's own tumour to detect residual or returning cancer after surgery. Medicare covers it in colorectal, breast, bladder, lung and ovarian cancer and for immunotherapy monitoring, and in 2026 it selected the bladder cancer patients for the first approval based on circulating tumour DNA."},{"id":"natera","kind":"company","name":"Natera","route":"/companies/natera/","tldr":"Natera makes Signatera, the dominant tumour-informed MRD test."},{"id":"mrd-testing","kind":"technology","name":"MRD / molecular residual disease testing","route":"/technologies/mrd-testing/","status":"established","tldr":"An ultra-sensitive blood test after surgery that detects leftover cancer months before a scan would."},{"id":"mrd","kind":"term","name":"Minimal / molecular residual disease (MRD)","route":"/terms/mrd/","tldr":"Cancer still present after treatment but too small to see on scans, detected by blood or marrow tests."},{"id":"tumour-informed-assay","kind":"term","name":"Tumour-informed versus tumour-naive ctDNA assays","route":"/terms/tumour-informed-assay/","tldr":"A tumour-informed blood test is built for one patient: the tumour is sequenced first and the test then hunts for that patient's own mutations in blood. A tumour-naive test uses the same fixed panel, often of methylation marks, for everyone, so it needs no tumour sample and returns faster."},{"id":"guardant-reveal","kind":"drug","name":"Guardant Reveal","route":"/drugs/guardant-reveal/","status":"established","tldr":"A blood test for leftover cancer after surgery that needs no tumour sample, so results come faster than tumour-informed tests."},{"id":"radar-mrd","kind":"drug","name":"RaDaR","route":"/drugs/radar-mrd/","status":"established","tldr":"NeoGenomics' personalised blood test for tiny amounts of leftover cancer, tracking up to 48 mutations from the patient's own tumour."},{"id":"paper-galaxy-signatera-nat-med-2023","kind":"paper","name":"GALAXY: tumour DNA in blood four weeks after bowel cancer surgery predicts relapse tenfold","route":"/key-papers/paper-galaxy-signatera-nat-med-2023/","tldr":"In 1,039 Japanese patients with resected colorectal cancer, a positive Signatera test at week 4 carried a tenfold higher recurrence risk, and only ctDNA-positive patients appeared to benefit from adjuvant chemotherapy."},{"id":"circulate-japan","kind":"trial","name":"CIRCULATE-Japan (GALAXY / VEGA / ALTAIR)","route":"/trials/circulate-japan/","status":"active","tldr":"Japan's national programme tests whether a blood test after surgery should decide who gets chemotherapy, and whether treating a positive test early helps."},{"id":"medicare-ced","kind":"term","name":"Medicare coverage with evidence development","route":"/terms/medicare-ced/","tldr":"Medicare's way of paying for a promising but uncertain test or treatment only for patients enrolled in a registry or study, used for PET scans in cancer from 2006 and now the frame for how Medicare covers gene panels and cell therapies."}],"trials":[{"id":"circulate-japan","name":"CIRCULATE-Japan (GALAXY / VEGA / ALTAIR)","route":"/trials/circulate-japan/","outcomes":[{"endpoint":"GALAXY (observational): recurrence risk by post-operative ctDNA status (4 weeks after surgery)","arms":[{"name":"ctDNA-positive","note":"n = 1,039 resectable stage II-IV CRC; ctDNA positivity was the strongest prognostic factor and identified who benefited from adjuvant chemotherapy (HR 6.59)"},{"name":"ctDNA-negative"}],"hr":10,"p":"<0.0001","source":"https://doi.org/10.1038/s41591-022-02115-4"},{"endpoint":"ALTAIR (randomised phase 3): disease-free survival in post-adjuvant ctDNA-positive patients","primary":true,"unit":"months","arms":[{"name":"Trifluridine/tipiracil","n":122,"value":9.3,"note":"Primary endpoint not met"},{"name":"Placebo","n":121,"value":5.55}],"hr":0.79,"ci":[0.6,1.05],"p":"0.107","source":"https://doi.org/10.1038/s41591-026-04428-0"}],"setting":"Resected stage II-IV colorectal cancer: ctDNA (Signatera) to guide adjuvant chemotherapy de-escalation (VEGA) or escalation with trifluridine/tipiracil (ALTAIR)","enrolledBasis":"registry"}],"papers":[{"id":"paper-galaxy-signatera-nat-med-2023","name":"GALAXY: tumour DNA in blood four weeks after bowel cancer surgery predicts relapse tenfold","route":"/key-papers/paper-galaxy-signatera-nat-med-2023/","journal":"Nature Medicine","year":2023,"whatItMeans":"The blood test stratifies risk far better than stage or pathology. It supports treating ctDNA-positive patients and suggests ctDNA-negative patients gain little from chemotherapy, but because treatment was not randomised the de-escalation claim needs the randomised trials that are now under way."}]},{"era":"2022-2026","title":"Randomised trials: sparing treatment works, adding it is harder","description":"DYNAMIC, published in June 2022, randomised 455 people with stage II colon cancer and cut adjuvant chemotherapy from 28 percent to 15 percent with two-year recurrence-free survival of 93.5 against 92.4 percent; the five-year update in 2025 held at 88 against 87 percent. Escalation has been harder to prove: ALTAIR, which gave trifluridine/tipiracil to ctDNA-positive patients after colorectal surgery, did not meet its disease-free survival endpoint, the MERMAID lung trials closed with 89 and 30 participants, and TRACC, BESPOKE and CIRCULATE-Japan's VEGA de-escalation trial are still running.","status":"current","refs":[{"id":"dynamic","kind":"trial","name":"DYNAMIC","route":"/trials/dynamic/","status":"positive","tldr":"Showed that a blood test can safely halve the number of colon cancer patients given chemotherapy after surgery."},{"id":"paper-dynamic-nejm-2022","kind":"paper","name":"DYNAMIC: a blood test safely halved chemotherapy use after surgery for stage II colon cancer","route":"/key-papers/paper-dynamic-nejm-2022/","tldr":"Giving chemotherapy only to patients with tumour DNA in their blood after surgery cut chemotherapy use from 28% to 15% with no loss in recurrence-free survival at two years."},{"id":"circulate-japan","kind":"trial","name":"CIRCULATE-Japan (GALAXY / VEGA / ALTAIR)","route":"/trials/circulate-japan/","status":"active","tldr":"Japan's national programme tests whether a blood test after surgery should decide who gets chemotherapy, and whether treating a positive test early helps."},{"id":"tracc","kind":"trial","name":"TRACC","route":"/trials/tracc/","status":"recruiting","tldr":"A UK study following 1,000 people after bowel cancer surgery with repeated blood tests for tumour DNA, to see how well a positive predicts the cancer coming back and whether the result can guide chemotherapy."},{"id":"bespoke-crc","kind":"trial","name":"BESPOKE CRC","route":"/trials/bespoke-crc/","status":"active","tldr":"Natera's US study in which 1,788 people with bowel cancer had Signatera blood tests after surgery and their doctors could act on the result; it records what changed and what happened, but does not randomise anyone."},{"id":"mermaid-1","kind":"trial","name":"MERMAID-1","route":"/trials/mermaid-1/","status":"completed","tldr":"A lung cancer trial that planned to test whether adding the immunotherapy durvalumab to chemotherapy after surgery helps people whose blood shows leftover tumour DNA; the registry lists it as complete with 89 participants."},{"id":"mermaid-2","kind":"trial","name":"MERMAID-2","route":"/trials/mermaid-2/","status":"completed","tldr":"A lung cancer trial that planned to start durvalumab the moment a surveillance blood test found tumour DNA, before any scan showed relapse; the registry lists it as complete with 30 participants."},{"id":"ctdna-mrd-to-adjuvant","kind":"pairing","name":"ctDNA MRD → adjuvant therapy decision","route":"/pairings/ctdna-mrd-to-adjuvant/","tldr":"A ctDNA MRD blood test after surgery decides who gets more treatment and who is spared it."},{"id":"de-escalation","kind":"term","name":"De-escalation, escalation and response-adapted therapy","route":"/terms/de-escalation/","tldr":"Giving less treatment to patients who are doing well and more to those who are not, using a marker such as scan response, ctDNA or MRD to decide. The aim is to cure the same number of people with less harm."},{"id":"trifluridine-tipiracil","kind":"drug","name":"Trifluridine/tipiracil","route":"/drugs/trifluridine-tipiracil/","status":"approved","tldr":"An oral chemotherapy pill for bowel cancer that has stopped responding to everything else; with bevacizumab it extends life by about three months."},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/","tldr":"The cancer where screening works best and where immunotherapy can make some tumours disappear entirely; chemotherapy still carries most metastatic disease, now with antibodies and targeted combinations chosen by RAS, BRAF, mismatch repair and which side of the bowel the tumour started on."}],"trials":[{"id":"dynamic","name":"DYNAMIC","route":"/trials/dynamic/","outcomes":[{"endpoint":"Recurrence-free survival at 2 years (non-inferiority)","primary":true,"unit":"%","arms":[{"name":"ctDNA-guided management","n":302,"value":93.5,"note":"Non-inferiority met (margin −8.5 points)"},{"name":"Standard management","n":153,"value":92.4}],"source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2200075"},{"endpoint":"Patients receiving adjuvant chemotherapy","unit":"%","arms":[{"name":"ctDNA-guided management","value":15},{"name":"Standard management","value":28}],"p":"<0.001","source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2200075"}],"setting":"Stage II colon cancer: ctDNA-guided adjuvant chemotherapy vs standard management","enrolled":455,"enrolledBasis":"registry"},{"id":"circulate-japan","name":"CIRCULATE-Japan (GALAXY / VEGA / ALTAIR)","route":"/trials/circulate-japan/","outcomes":[{"endpoint":"GALAXY (observational): recurrence risk by post-operative ctDNA status (4 weeks after surgery)","arms":[{"name":"ctDNA-positive","note":"n = 1,039 resectable stage II-IV CRC; ctDNA positivity was the strongest prognostic factor and identified who benefited from adjuvant chemotherapy (HR 6.59)"},{"name":"ctDNA-negative"}],"hr":10,"p":"<0.0001","source":"https://doi.org/10.1038/s41591-022-02115-4"},{"endpoint":"ALTAIR (randomised phase 3): disease-free survival in post-adjuvant ctDNA-positive patients","primary":true,"unit":"months","arms":[{"name":"Trifluridine/tipiracil","n":122,"value":9.3,"note":"Primary endpoint not met"},{"name":"Placebo","n":121,"value":5.55}],"hr":0.79,"ci":[0.6,1.05],"p":"0.107","source":"https://doi.org/10.1038/s41591-026-04428-0"}],"setting":"Resected stage II-IV colorectal cancer: ctDNA (Signatera) to guide adjuvant chemotherapy de-escalation (VEGA) or escalation with trifluridine/tipiracil (ALTAIR)","enrolledBasis":"registry"},{"id":"mermaid-2","name":"MERMAID-2","route":"/trials/mermaid-2/","outcomes":[{"endpoint":"Disease-free Survival (DFS)","primary":true,"unit":"months","arms":[{"name":"Durvalumab","n":15,"value":3.9,"note":"95% CI 3.515 to NA; Figures from the ClinicalTrials.gov results section (first posted 2024-06-25), not from a publication"},{"name":"Placebo","n":15,"value":2,"note":"95% CI 1.643 to 3.910"}],"source":"https://clinicaltrials.gov/study/NCT04642469?tab=results"}],"setting":"Stage II to III non-small-cell lung cancer after surgery and curative treatment: durvalumab against placebo started when ctDNA becomes detectable during surveillance","enrolled":30,"enrolledBasis":"registry"}],"papers":[{"id":"paper-dynamic-nejm-2022","name":"DYNAMIC: a blood test safely halved chemotherapy use after surgery for stage II colon cancer","route":"/key-papers/paper-dynamic-nejm-2022/","journal":"New England Journal of Medicine","year":2022,"whatItMeans":"For stage II colon cancer, where most patients are cured by surgery alone, a blood test can identify the minority who benefit from chemotherapy and spare everyone else its side effects. It does not yet prove that treating ctDNA-positive patients improves survival compared with not treating them."}]},{"era":"2025-2026","title":"The first drug approval that depends on a ctDNA result","description":"IMvigor011 tested 761 people after cystectomy for muscle-invasive bladder cancer and randomised the 250 whose blood turned ctDNA-positive to atezolizumab or placebo: disease-free survival hazard ratio 0.64 and overall survival hazard ratio 0.59, published in NEJM in December 2025. On 15 May 2026 the FDA approved adjuvant atezolizumab for patients with ctDNA molecular residual disease after cystectomy, with Signatera CDx as the companion diagnostic, so a residual disease blood test now sits inside a drug label.","status":"current","refs":[{"id":"imvigor011","kind":"trial","name":"IMvigor011","route":"/trials/imvigor011/","status":"positive","tldr":"The first trial to use a blood test for leftover cancer to decide who gets immunotherapy, and it worked."},{"id":"paper-imvigor011-nejm-2025","kind":"paper","name":"IMvigor011: using a blood test for leftover cancer to decide who gets immunotherapy after bladder surgery","route":"/key-papers/paper-imvigor011-nejm-2025/","tldr":"Patients whose blood turned positive for tumour DNA after cystectomy lived longer with atezolizumab than placebo; patients who stayed ctDNA-negative did well without any treatment. It is the first ctDNA-guided adjuvant trial to improve survival."},{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/","status":"approved","tldr":"A PD-L1 blocker used in lung, liver, and bladder cancer. In 2026 it became the first drug approved based on a blood test showing leftover cancer after bladder surgery."},{"id":"signatera","kind":"drug","name":"Signatera","route":"/drugs/signatera/","status":"established","tldr":"Signatera is Natera's tumour-informed blood test that tracks 16 mutations from each patient's own tumour to detect residual or returning cancer after surgery. Medicare covers it in colorectal, breast, bladder, lung and ovarian cancer and for immunotherapy monitoring, and in 2026 it selected the bladder cancer patients for the first approval based on circulating tumour DNA."},{"id":"thomas-powles","kind":"person","name":"Thomas Powles","route":"/people/thomas-powles/","tldr":"Led EV-302, NIAGARA and IMvigor011, the trials that transformed bladder cancer from chemotherapy-only to ADC, immunotherapy and ctDNA-guided care."},{"id":"urothelial","kind":"cancer","name":"Bladder & urothelial cancer","route":"/cancers/urothelial/","tldr":"Bladder cancer went from 40 years of cisplatin to an ADC-immunotherapy combination that nearly doubled survival, and in 2026 the first blood-test-guided drug approval."},{"id":"companion-diagnostic","kind":"technology","name":"Companion diagnostics","route":"/technologies/companion-diagnostic/","status":"standard-of-care","tldr":"The test that decides whether a specific drug is right for you, approved together with the drug."}],"trials":[{"id":"imvigor011","name":"IMvigor011","route":"/trials/imvigor011/","outcomes":[{"endpoint":"Disease-free survival (ctDNA-positive, randomised)","primary":true,"unit":"months","arms":[{"name":"Atezolizumab","n":167,"value":9.9},{"name":"Placebo","n":83,"value":4.8}],"hr":0.64,"ci":[0.47,0.88],"p":"0.005","source":"https://www.roche.com/media/releases/med-cor-2025-10-20b"},{"endpoint":"Overall survival (ctDNA-positive)","unit":"months","arms":[{"name":"Atezolizumab","value":32.8},{"name":"Placebo","value":21.1}],"hr":0.59,"ci":[0.41,0.86],"p":"0.005","source":"https://www.roche.com/media/releases/med-cor-2025-10-20b"},{"endpoint":"Disease-free survival at 12 months, persistently ctDNA-negative (untreated surveillance)","unit":"%","arms":[{"name":"ctDNA-negative, surveillance only","n":357,"value":95.4,"note":"12-month OS 100% in this group"}],"source":"https://www.roche.com/media/releases/med-cor-2025-10-20b"}],"setting":"Muscle-invasive bladder cancer after cystectomy, ctDNA-positive (Signatera): atezolizumab vs placebo","enrolled":761,"enrolledBasis":"registry"}],"papers":[{"id":"paper-imvigor011-nejm-2025","name":"IMvigor011: using a blood test for leftover cancer to decide who gets immunotherapy after bladder surgery","route":"/key-papers/paper-imvigor011-nejm-2025/","journal":"New England Journal of Medicine","year":2025,"whatItMeans":"After bladder removal, a blood test can now tell who needs immunotherapy and who can safely be spared it. This is the model for MRD-guided adjuvant therapy across cancers: treat the blood-positive, watch the blood-negative."}]},{"era":"2021-2026","title":"Screening from blood: one cancer approved, many cancers under review","description":"PATHFINDER, published in 2023, was the first prospective test of a multi-cancer blood test in 6,621 adults without symptoms: 1.4 percent had a signal, 38 percent of those had cancer, and resolving a positive took a median of 79 days. Shield became the first FDA-approved blood test for colorectal cancer screening on 26 July 2024, for average-risk adults aged 45 and over with colonoscopy after a positive. NHS-Galleri, the randomised trial of Galleri in 142,250 people in England, reported on 30 May 2026 that stage III and IV cancers combined were not reduced (the primary endpoint) while stage IV diagnoses fell by 14 percent; PATHFINDER 2 reported a positive predictive value of 60.3 percent in 35,878 people the next day, and GRAIL's premarket application, filed on 29 January 2026, goes to an FDA advisory panel on 23 September 2026. The trial's peer-reviewed test-performance paper appeared in Nature Medicine on 22 September 2026: positive results in 1.03, 0.80 and 0.90 percent of intervention-arm participants across three annual rounds, positive predictive values of 58.0, 50.4 and 45.8 percent, specificity of 99.50 to 99.60 percent and episode sensitivity of 26.7 to 37.2 percent for all cancers; it states the primary endpoint was not met and is reported elsewhere.","status":"current","refs":[{"id":"mced","kind":"technology","name":"Multi-cancer early detection (MCED)","route":"/technologies/mced/","status":"phase-3","tldr":"A single blood test intended to screen for dozens of cancers at once, including ones with no screening today."},{"id":"galleri","kind":"drug","name":"Galleri","route":"/drugs/galleri/","status":"phase-3","tldr":"A blood test screening for more than 50 cancers at once, before the FDA in September 2026."},{"id":"shield","kind":"drug","name":"Shield","route":"/drugs/shield/","status":"approved","tldr":"The first FDA-approved blood test for colorectal cancer screening (2024), now optionally reporting other cancers too."},{"id":"grail","kind":"company","name":"GRAIL","route":"/companies/grail/","tldr":"GRAIL developed Galleri, the multi-cancer blood test awaiting an FDA decision after a September 2026 advisory committee."},{"id":"guardant-health","kind":"company","name":"Guardant Health","route":"/companies/guardant-health/","tldr":"Liquid biopsy leader: Guardant360 for genotyping, Reveal for MRD, Shield for screening."},{"id":"pathfinder-2","kind":"trial","name":"PATHFINDER 2","route":"/trials/pathfinder-2/","status":"active","tldr":"PATHFINDER 2 is the US real-world study of the Galleri test that forms the core of its FDA submission."},{"id":"nhs-galleri","kind":"trial","name":"NHS-Galleri","route":"/trials/nhs-galleri/","status":"active","tldr":"The largest cancer screening trial ever run, testing whether a multi-cancer blood test reduces late-stage diagnoses; it reports that it did not, and its test-performance paper appeared in Nature Medicine on 22 September 2026."},{"id":"eclipse-shield","kind":"trial","name":"ECLIPSE (Shield blood test)","route":"/trials/eclipse-shield/","status":"positive","tldr":"The study behind the first approved blood test for bowel cancer screening: it found 83% of cancers but only 13% of advanced polyps."},{"id":"paper-pathfinder-lancet-2023","kind":"paper","name":"PATHFINDER: the first prospective test of a multi-cancer blood test in people without symptoms","route":"/key-papers/paper-pathfinder-lancet-2023/","tldr":"In 6,621 adults over 50, the Galleri test flagged a cancer signal in 1.4%, of whom 38% turned out to have cancer; diagnostic work-up took about two months for true positives and over five months for false positives."},{"id":"paper-nhs-galleri-design-cancers-2022","kind":"paper","name":"NHS-Galleri: design of the largest randomised trial of a multi-cancer blood test","route":"/key-papers/paper-nhs-galleri-design-cancers-2022/","tldr":"The NHS-Galleri design paper is the protocol for a 140,000-person randomised trial in England testing whether three annual Galleri blood tests reduce late-stage (III-IV) cancer diagnoses, the first MCED trial powered for a stage-shift endpoint."},{"id":"paper-nhs-galleri-performance-nat-med-2026","kind":"paper","name":"Performance of a multi-cancer early detection test in the randomized controlled NHS-Galleri trial","route":"/key-papers/paper-nhs-galleri-performance-nat-med-2026/","tldr":"In the NHS-Galleri trial about one person in a hundred had a positive blood test in each of three yearly rounds, roughly half of those positives were cancer, and the test missed most cancers diagnosed during the trial. The paper says the main endpoint, fewer late-stage diagnoses, was not met and is reported elsewhere."},{"id":"cfdna-methylation-testing","kind":"technology","name":"Cell-free DNA methylation tests","route":"/technologies/cfdna-methylation-testing/","status":"approved","tldr":"Blood tests that read chemical marks on fragments of DNA shed by tumours; the marks tell cancer DNA from normal DNA and hint at where the cancer is."},{"id":"stage-shift","kind":"term","name":"Stage shift","route":"/terms/stage-shift/","tldr":"Stage shift means finding more cancers early and fewer late; it is the measurable goal of screening."},{"id":"ppv","kind":"term","name":"Positive predictive value (PPV)","route":"/terms/ppv/","tldr":"Positive predictive value (PPV) is the chance that a positive test result is actually right: true positives divided by all positives. Because it falls as a disease becomes rarer, even a specific screening test gives mostly false alarms when prevalence is low, which is why PPV decides whether a multi-cancer blood test is useful."},{"id":"deb-schrag","kind":"person","name":"Deborah Schrag","route":"/people/deb-schrag/","tldr":"Led PATHFINDER, the first prospective study of a multi-cancer blood test in practice, and the PROSPECT rectal cancer trial."},{"id":"peter-sasieni","kind":"person","name":"Peter Sasieni","route":"/people/peter-sasieni/","tldr":"Epidemiologist who showed HPV vaccination has nearly eliminated cervical cancer in vaccinated English women and leads NHS-Galleri."}],"trials":[{"id":"pathfinder-2","name":"PATHFINDER 2","route":"/trials/pathfinder-2/","outcomes":[{"endpoint":"Cancer signal detected","unit":"%","arms":[{"name":"Galleri, all participants","n":25578,"value":0.93}],"source":"https://clinicaltrials.gov/study/NCT05155605"},{"endpoint":"Positive predictive value","unit":"%","arms":[{"name":"Galleri","value":61.6}],"source":"https://clinicaltrials.gov/study/NCT05155605"},{"endpoint":"Specificity","unit":"%","arms":[{"name":"Galleri","value":99.6}],"source":"https://clinicaltrials.gov/study/NCT05155605"}],"setting":"~35,000 adults ≥50 receiving Galleri alongside standard screening, single-arm","enrolled":35883,"enrolledBasis":"registry"},{"id":"nhs-galleri","name":"NHS-Galleri","route":"/trials/nhs-galleri/","outcomes":[{"endpoint":"Stage III to IV incidence, 12 prespecified cancers (primary)","primary":true,"arms":[{"name":"Galleri + usual NHS care","note":"Not met, per the Nature Medicine test-performance paper (22 September 2026), which states the primary endpoint was not met and reported elsewhere; no peer-reviewed primary-endpoint paper was on Europe PMC by 23 September 2026, so no figures are recorded here."},{"name":"Usual NHS care"}],"source":"https://doi.org/10.1038/s41591-026-04652-8"},{"endpoint":"Positive test results by screening round","unit":"%","arms":[{"name":"Round 1","n":70325,"value":1.03,"note":"722, 518 and 561 positive results among evaluable intervention-arm participants"},{"name":"Round 2","n":64498,"value":0.8},{"name":"Round 3","n":62323,"value":0.9}],"source":"https://doi.org/10.1038/s41591-026-04652-8"},{"endpoint":"Cancer detection rate by screening round","unit":"%","arms":[{"name":"Round 1","n":70325,"value":0.6,"note":"937 participants had MCED-detected primary cancers across the three rounds"},{"name":"Round 2","n":64498,"value":0.4},{"name":"Round 3","n":62323,"value":0.41}],"source":"https://doi.org/10.1038/s41591-026-04652-8"},{"endpoint":"Positive predictive value by screening round","unit":"%","arms":[{"name":"Round 1","n":722,"value":58,"note":"419/722, 261/518 and 257/561"},{"name":"Round 2","n":518,"value":50.4},{"name":"Round 3","n":561,"value":45.8}],"source":"https://doi.org/10.1038/s41591-026-04652-8"},{"endpoint":"Negative predictive value by screening round","unit":"%","arms":[{"name":"Round 1","n":69603,"value":98.98,"note":"68,895/69,603, 63,278/63,980 and 61,058/61,762"},{"name":"Round 2","n":63980,"value":98.9},{"name":"Round 3","n":61762,"value":98.86}],"source":"https://doi.org/10.1038/s41591-026-04652-8"},{"endpoint":"Specificity, range across rounds","unit":"%","arms":[{"name":"Lowest round","value":99.5,"note":"The abstract gives the range across rounds 1 to 3, not per-round values"},{"name":"Highest round","value":99.6}],"source":"https://doi.org/10.1038/s41591-026-04652-8"},{"endpoint":"Episode sensitivity, all cancers, range across rounds","unit":"%","arms":[{"name":"Lowest round","value":26.7,"note":"Range across rounds 1 to 3 as given in the abstract"},{"name":"Highest round","value":37.2}],"source":"https://doi.org/10.1038/s41591-026-04652-8"},{"endpoint":"Episode sensitivity, 12 prespecified cancer types, range across rounds","unit":"%","arms":[{"name":"Lowest round","value":47.6,"note":"Range across rounds 1 to 3 as given in the abstract"},{"name":"Highest round","value":63.4}],"source":"https://doi.org/10.1038/s41591-026-04652-8"},{"endpoint":"Cancer signal origin accuracy, range across rounds","unit":"%","arms":[{"name":"Lowest round","value":91.1},{"name":"Highest round","value":93.6}],"source":"https://doi.org/10.1038/s41591-026-04652-8"},{"endpoint":"Relative reduction in stage IV diagnoses, rounds 2 and 3","unit":"%","arms":[{"name":"Round 2","value":22,"note":"Relative reduction versus control in the 12 prespecified cancers, from GRAIL's release of 30 May 2026; not in the Nature Medicine paper"},{"name":"Round 3","value":26}],"source":"https://grail.com/press-releases/grail-reports-full-results-from-nhs-galleri-trial-demonstrating-substantial-reduction-in-stage-iv-cancer-diagnoses-at-2026-asco-annual-meeting/"},{"endpoint":"Relative reduction in diagnosis through emergency presentation","unit":"%","arms":[{"name":"Galleri + standard screening","value":25,"note":"From GRAIL's release of 30 May 2026; not in the Nature Medicine paper"}],"source":"https://grail.com/press-releases/grail-reports-full-results-from-nhs-galleri-trial-demonstrating-substantial-reduction-in-stage-iv-cancer-diagnoses-at-2026-asco-annual-meeting/"}],"setting":"142,250 asymptomatic adults aged 50 to 77 in England, randomised 1:1 to three annual rounds of the Galleri multi-cancer early detection blood test added to usual NHS care, or to blood draws stored without results","enrolled":142250,"enrolledNote":"ClinicalTrials.gov NCT05611632 and ISRCTN91431511 list 142,318 participants (actual); the Nature Medicine test-performance paper reports 142,250 participants randomised 1:1.","enrolledBasis":"randomised"},{"id":"eclipse-shield","name":"ECLIPSE (Shield blood test)","route":"/trials/eclipse-shield/","outcomes":[{"endpoint":"Sensitivity for colorectal cancer","primary":true,"unit":"%","arms":[{"name":"Shield cfDNA blood test","value":83.1}],"source":"https://doi.org/10.1056/NEJMoa2304714"},{"endpoint":"Specificity for advanced neoplasia","primary":true,"unit":"%","arms":[{"name":"Shield cfDNA blood test","value":89.6}],"source":"https://doi.org/10.1056/NEJMoa2304714"}],"setting":"Prospective study of the Shield cell-free DNA blood test against screening colonoscopy in average-risk adults aged 45 to 84","enrolled":44467,"enrolledBasis":"registry"}],"papers":[{"id":"paper-pathfinder-lancet-2023","name":"PATHFINDER: the first prospective test of a multi-cancer blood test in people without symptoms","route":"/key-papers/paper-pathfinder-lancet-2023/","journal":"The Lancet","year":2023,"whatItMeans":"A multi-cancer blood test can be run in ordinary clinics, and most positive results can be resolved with imaging. But six in ten positives are false alarms that take months to resolve, and the test misses most cancers. Whether it reduces late-stage cancer or deaths is unknown; that requires randomised trials."},{"id":"paper-nhs-galleri-design-cancers-2022","name":"NHS-Galleri: design of the largest randomised trial of a multi-cancer blood test","route":"/key-papers/paper-nhs-galleri-design-cancers-2022/","journal":"Cancers","year":2022,"whatItMeans":"NHS-Galleri is the trial that will decide whether a blood test for many cancers at once should be offered by a health system. Its endpoint is a reduction in late-stage cancer rather than deaths, so even a positive result leaves the mortality question to be settled by longer follow-up."},{"id":"paper-nhs-galleri-performance-nat-med-2026","name":"Performance of a multi-cancer early detection test in the randomized controlled NHS-Galleri trial","route":"/key-papers/paper-nhs-galleri-performance-nat-med-2026/","journal":"Nature Medicine","year":2026,"whatItMeans":"For someone offered the test, these are the numbers that describe what a result means in an NHS population: about 1 in 100 tests came back positive each year, between 46 and 58 in 100 positives were cancer, and a negative result left about 1 in 100 with an undetected cancer within the year. The test found between a quarter and a third of all cancers diagnosed in a screening round, and about half to two thirds of the 12 cancer types it was designed to find. Whether finding them this way reduces late-stage diagnoses is the primary question, and this paper says only that the answer was no; the primary-endpoint paper had not appeared on Europe PMC by 23 September 2026."}]},{"era":"2026-2029","title":"The randomised answers arrive","description":"The open questions each have a trial with a date on the registry. For screening, the NCI's Vanguard study randomises 24,000 people to multi-cancer detection tests or usual care, with primary completion listed for 31 January 2029, and NHS-Galleri's follow-up continues. For residual disease, CIRCULATE-US randomises stage III colon cancer patients by Signatera result to more or less chemotherapy (primary completion 10 March 2029), TRACC follows 1,000 people to 2029, and VEGA asks whether ctDNA-negative patients can skip chemotherapy altogether. If escalation trials keep missing, the field's case will rest on de-escalation and on ctDNA as a surrogate endpoint.","status":"emerging","refs":[{"id":"vanguard-study","kind":"trial","name":"Vanguard Study (NCI Cancer Screening Research Network)","route":"/trials/vanguard-study/","status":"recruiting","tldr":"The US government's first randomised study of multi-cancer blood tests: 24,000 people are being assigned to a blood test or usual care to work out how a much larger trial should be run."},{"id":"circulate-us","kind":"trial","name":"CIRCULATE-US","route":"/trials/circulate-us/","status":"recruiting","tldr":"The US national trial that uses a blood test for leftover tumour DNA to decide who gets less chemotherapy and who gets more after stage III colon cancer surgery, with both questions randomised."},{"id":"tracc","kind":"trial","name":"TRACC","route":"/trials/tracc/","status":"recruiting","tldr":"A UK study following 1,000 people after bowel cancer surgery with repeated blood tests for tumour DNA, to see how well a positive predicts the cancer coming back and whether the result can guide chemotherapy."},{"id":"circulate-japan","kind":"trial","name":"CIRCULATE-Japan (GALAXY / VEGA / ALTAIR)","route":"/trials/circulate-japan/","status":"active","tldr":"Japan's national programme tests whether a blood test after surgery should decide who gets chemotherapy, and whether treating a positive test early helps."},{"id":"nci","kind":"institution","name":"National Cancer Institute (NIH)","route":"/institutions/nci/","tldr":"The NCI is the US government's cancer research agency, spending ~$7B a year and running the Cancer Centers Program, TCGA, and Rosenberg's cell therapy lab."},{"id":"nrg-oncology","kind":"company","name":"NRG Oncology","route":"/companies/nrg-oncology/","tldr":"The US cooperative group formed from the radiation, gynaecologic, and breast trial groups; it co-led OlympiA, the trial that put a PARP inhibitor after surgery for BRCA carriers."},{"id":"idea-ctdna-guided-adjuvant-crc","kind":"idea","name":"ctDNA-guided adjuvant therapy as the default in stage II-III colon cancer","route":"/ideas/idea-ctdna-guided-adjuvant-crc/","tldr":"Use a blood test after surgery to decide who gets chemotherapy: spare the negatives, and find something that actually works for the positives."},{"id":"idea-tr2-ctdna-mrd-qualification","kind":"idea","name":"Formally qualify tumour-DNA blood tests as a surrogate endpoint for adjuvant trials","route":"/ideas/idea-tr2-ctdna-mrd-qualification/","tldr":"If a blood test reliably shows whether cancer will come back after surgery, trials could use it instead of waiting years for relapse. Regulators have a process to bless such a test; oncology should use it."},{"id":"surrogate-validation","kind":"term","name":"Surrogate endpoint validation: which stand-ins have earned trust","route":"/terms/surrogate-validation/","tldr":"A surrogate endpoint only deserves trust if trials have shown that moving it moves the outcome that matters, in that disease and for that kind of drug; some stand-ins have passed that test, several have not, and the record differs endpoint by endpoint."}],"trials":[{"id":"circulate-japan","name":"CIRCULATE-Japan (GALAXY / VEGA / ALTAIR)","route":"/trials/circulate-japan/","outcomes":[{"endpoint":"GALAXY (observational): recurrence risk by post-operative ctDNA status (4 weeks after surgery)","arms":[{"name":"ctDNA-positive","note":"n = 1,039 resectable stage II-IV CRC; ctDNA positivity was the strongest prognostic factor and identified who benefited from adjuvant chemotherapy (HR 6.59)"},{"name":"ctDNA-negative"}],"hr":10,"p":"<0.0001","source":"https://doi.org/10.1038/s41591-022-02115-4"},{"endpoint":"ALTAIR (randomised phase 3): disease-free survival in post-adjuvant ctDNA-positive patients","primary":true,"unit":"months","arms":[{"name":"Trifluridine/tipiracil","n":122,"value":9.3,"note":"Primary endpoint not met"},{"name":"Placebo","n":121,"value":5.55}],"hr":0.79,"ci":[0.6,1.05],"p":"0.107","source":"https://doi.org/10.1038/s41591-026-04428-0"}],"setting":"Resected stage II-IV colorectal cancer: ctDNA (Signatera) to guide adjuvant chemotherapy de-escalation (VEGA) or escalation with trifluridine/tipiracil (ALTAIR)","enrolledBasis":"registry"}],"papers":[]},{"era":"2026-2030","title":"Deeper, cheaper and tumour-naive","description":"Two technical routes are competing to make the tests more sensitive without a tumour sample: methylation, which reads chemical marks that also point to the tissue of origin, and fragmentomics, which reads the sizes and positions of the fragments themselves. Whole-genome approaches and repeated sampling aim to catch relapse earlier than a three-monthly draw. The gating question for all of them is utility rather than sensitivity: finding disease earlier has to change an outcome, and the clonal haematopoiesis of normal blood cells is the main source of false positives.","status":"emerging","refs":[{"id":"cfdna-methylation-testing","kind":"technology","name":"Cell-free DNA methylation tests","route":"/technologies/cfdna-methylation-testing/","status":"approved","tldr":"Blood tests that read chemical marks on fragments of DNA shed by tumours; the marks tell cancer DNA from normal DNA and hint at where the cancer is."},{"id":"fragmentomics","kind":"technology","name":"cfDNA fragmentomics","route":"/technologies/fragmentomics/","status":"established","tldr":"Fragmentomics reads the sizes and positions of DNA fragments in blood, not the mutations. Cancer cells die messily and leave a recognisable fragmentation pattern."},{"id":"methylation-profiling","kind":"technology","name":"DNA methylation profiling","route":"/technologies/methylation-profiling/","status":"established","tldr":"Reading chemical tags on DNA that reveal a cell's identity, used to classify brain tumours and to detect cancer in blood."},{"id":"continuous-ctdna-monitoring","kind":"technology","name":"Continuous and near-continuous ctDNA monitoring","route":"/technologies/continuous-ctdna-monitoring/","status":"concept","tldr":"Instead of testing blood every three months, sampling constantly, so a relapse is caught the week it starts."},{"id":"delfi-diagnostics","kind":"company","name":"DELFI Diagnostics","route":"/companies/delfi-diagnostics/","tldr":"Fragmentomics company whose FirstLook Lung blood test aims to raise lung-cancer screening uptake; first randomised clinical-utility data in 2026."},{"id":"freenome","kind":"company","name":"Freenome","route":"/companies/freenome/","tldr":"Freenome makes SimpleScreen CRC, the second FDA-approved blood test for colorectal cancer screening (July 2026), commercialised by Abbott."},{"id":"guardant-reveal","kind":"drug","name":"Guardant Reveal","route":"/drugs/guardant-reveal/","status":"established","tldr":"A blood test for leftover cancer after surgery that needs no tumour sample, so results come faster than tumour-informed tests."},{"id":"clonal-haematopoiesis","kind":"pathway","name":"Clonal haematopoiesis (CHIP)","route":"/pathways/clonal-haematopoiesis/","tldr":"As we age, blood stem cells with cancer-like mutations quietly expand in most people. These clones raise leukaemia and heart disease risk, are accelerated by chemotherapy, and confuse blood tests for cancer DNA."},{"id":"mrd-kinetics-models","kind":"technology","name":"Residual disease kinetics (BCR-ABL halving and ctDNA slopes)","route":"/technologies/mrd-kinetics-models/","status":"established","tldr":"The speed at which a molecular marker falls during treatment predicts outcome better than a single level: BCR-ABL halving time in chronic myeloid leukaemia and circulating tumour DNA slopes in solid tumours are now used to judge response within weeks."},{"id":"idea-bio2-whole-genome-mrd-depth","kind":"idea","name":"Push residual disease detection a hundredfold deeper with whole-genome methods","route":"/ideas/idea-bio2-whole-genome-mrd-depth/","tldr":"Current blood tests for leftover cancer track a few dozen mutations and miss low-level disease. Whole-genome and error-corrected methods integrate signal across thousands of tumour-specific sites plus methylation and fragment features, reaching detection near one part per million in research settings; cost, turnaround and reproducibility are the barriers."},{"id":"idea-bio1-methylation-clone-tracking","kind":"idea","name":"Track clones in blood with methylation patterns instead of mutations","route":"/ideas/idea-bio1-methylation-clone-tracking/","tldr":"Tumour DNA in blood can be told apart by chemical marks as well as mutations. Marks are more numerous and cheaper to read, so they could track more sub-populations for less money."}],"trials":[],"papers":[]},{"era":"What sets the pace","title":"Payment, standards and what to do with a positive","description":"In the United States, Medicare pays for residual disease tests through a MolDX coverage article that names tests and cancers one at a time (revision effective 1 January 2026); screening tests need their own coverage route, and most health systems outside the United States pay for none of this yet. Laboratories run different assays with no shared reference material, so a positive in one is not a positive in another, and a screening positive still needs a fast, agreed diagnostic pathway. Coverage with evidence, reference plasma standards and a national positive-result pathway are the proposals on the table.","status":"current","refs":[{"id":"medicare-ced","kind":"term","name":"Medicare coverage with evidence development","route":"/terms/medicare-ced/","tldr":"Medicare's way of paying for a promising but uncertain test or treatment only for patients enrolled in a registry or study, used for PET scans in cancer from 2006 and now the frame for how Medicare covers gene panels and cell therapies."},{"id":"fda-ldt-rule","kind":"term","name":"FDA laboratory-developed test (LDT) rule","route":"/terms/fda-ldt-rule/","tldr":"Most cancer tests in the US, including Galleri, Signatera and Oncotype DX, are 'lab-developed tests' overseen through lab standards rather than FDA approval; the FDA's 2024 attempt to change that was struck down in court in 2025."},{"id":"idea-bio2-mrd-coverage-with-evidence","kind":"idea","name":"Pay for residual disease tests only inside a trial or registry","route":"/ideas/idea-bio2-mrd-coverage-with-evidence/","tldr":"Leftover-cancer blood tests are being sold faster than evidence that acting on them helps. Paying for them only when the result is recorded would generate the missing evidence."},{"id":"idea-tr2-ctdna-reference-plasma","kind":"idea","name":"Certified reference samples to benchmark every tumour-DNA blood test","route":"/ideas/idea-tr2-ctdna-reference-plasma/","tldr":"Dozens of companies sell blood tests for tumour DNA and they report different results on the same sample. Government-issued reference samples with known amounts of tumour DNA would expose the differences."},{"id":"idea-bio2-mrd-reference-standards","kind":"idea","name":"Reference materials and open proficiency testing for residual disease tests","route":"/ideas/idea-bio2-mrd-reference-standards/","tldr":"Different companies' leftover-cancer blood tests disagree, and there is no shared yardstick. Public reference samples would let anyone check which test actually works."},{"id":"idea-prev-mced-positive-resolution-pathway","kind":"idea","name":"A 28-day national pathway for people with a positive multi-cancer blood test","route":"/ideas/idea-prev-mced-positive-resolution-pathway/","tldr":"A positive blood test with no known tumour is frightening and hard to manage. A standard imaging cascade with a time limit, and a registry of what was found, would make these tests usable."},{"id":"b-dormancy-mrd","kind":"bottleneck","name":"Dormant cells and minimal residual disease","route":"/bottlenecks/b-dormancy-mrd/","tldr":"After a 'successful' treatment, cells can sleep for years then relapse. We can barely detect them and cannot target them."}],"trials":[],"papers":[]}],"watch":[{"item":"FDA Molecular and Clinical Genetics Panel reviews the Galleri premarket approval application","expected":"2026-09-23","source":"https://grail.com/press-releases/grail-announces-fda-advisory-committee-meeting-to-review-premarket-approval-application-for-the-galleri-multi-cancer-early-detection-test/","refs":[{"id":"galleri","kind":"drug","name":"Galleri","route":"/drugs/galleri/","status":"phase-3","tldr":"A blood test screening for more than 50 cancers at once, before the FDA in September 2026."},{"id":"grail","kind":"company","name":"GRAIL","route":"/companies/grail/","tldr":"GRAIL developed Galleri, the multi-cancer blood test awaiting an FDA decision after a September 2026 advisory committee."},{"id":"mced","kind":"technology","name":"Multi-cancer early detection (MCED)","route":"/technologies/mced/","status":"phase-3","tldr":"A single blood test intended to screen for dozens of cancers at once, including ones with no screening today."}]},{"item":"IMvigor011 study completion on the registry; longer follow-up of ctDNA-negative patients under surveillance","expected":"2026-10-01","source":"https://clinicaltrials.gov/study/NCT04660344","refs":[{"id":"imvigor011","kind":"trial","name":"IMvigor011","route":"/trials/imvigor011/","status":"positive","tldr":"The first trial to use a blood test for leftover cancer to decide who gets immunotherapy, and it worked."},{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/","status":"approved","tldr":"A PD-L1 blocker used in lung, liver, and bladder cancer. In 2026 it became the first drug approved based on a blood test showing leftover cancer after bladder surgery."}]},{"item":"NHS-Galleri: peer-reviewed test-performance paper (reported: Nature Medicine, 22 September 2026, states the primary endpoint was not met and is reported elsewhere)","expected":"2026-09-22","source":"https://doi.org/10.1038/s41591-026-04652-8","refs":[{"id":"nhs-galleri","kind":"trial","name":"NHS-Galleri","route":"/trials/nhs-galleri/","status":"active","tldr":"The largest cancer screening trial ever run, testing whether a multi-cancer blood test reduces late-stage diagnoses; it reports that it did not, and its test-performance paper appeared in Nature Medicine on 22 September 2026."},{"id":"galleri","kind":"drug","name":"Galleri","route":"/drugs/galleri/","status":"phase-3","tldr":"A blood test screening for more than 50 cancers at once, before the FDA in September 2026."},{"id":"stage-shift","kind":"term","name":"Stage shift","route":"/terms/stage-shift/","tldr":"Stage shift means finding more cancers early and fewer late; it is the measurable goal of screening."},{"id":"paper-nhs-galleri-performance-nat-med-2026","kind":"paper","name":"Performance of a multi-cancer early detection test in the randomized controlled NHS-Galleri trial","route":"/key-papers/paper-nhs-galleri-performance-nat-med-2026/","tldr":"In the NHS-Galleri trial about one person in a hundred had a positive blood test in each of three yearly rounds, roughly half of those positives were cancer, and the test missed most cancers diagnosed during the trial. The paper says the main endpoint, fewer late-stage diagnoses, was not met and is reported elsewhere."}]},{"item":"NHS-Galleri: primary-endpoint paper (stage III/IV incidence) not yet on Europe PMC; registry study completion, with cancer-specific mortality follow-up, listed as January 2031","expected":"2031-01","source":"https://clinicaltrials.gov/study/NCT05611632","refs":[{"id":"nhs-galleri","kind":"trial","name":"NHS-Galleri","route":"/trials/nhs-galleri/","status":"active","tldr":"The largest cancer screening trial ever run, testing whether a multi-cancer blood test reduces late-stage diagnoses; it reports that it did not, and its test-performance paper appeared in Nature Medicine on 22 September 2026."},{"id":"galleri","kind":"drug","name":"Galleri","route":"/drugs/galleri/","status":"phase-3","tldr":"A blood test screening for more than 50 cancers at once, before the FDA in September 2026."},{"id":"stage-shift","kind":"term","name":"Stage shift","route":"/terms/stage-shift/","tldr":"Stage shift means finding more cancers early and fewer late; it is the measurable goal of screening."}]},{"item":"ECLIPSE (Shield) study completion on the registry","expected":"2027-08-05","source":"https://clinicaltrials.gov/study/NCT04136002","refs":[{"id":"eclipse-shield","kind":"trial","name":"ECLIPSE (Shield blood test)","route":"/trials/eclipse-shield/","status":"positive","tldr":"The study behind the first approved blood test for bowel cancer screening: it found 83% of cancers but only 13% of advanced polyps."},{"id":"shield","kind":"drug","name":"Shield","route":"/drugs/shield/","status":"approved","tldr":"The first FDA-approved blood test for colorectal cancer screening (2024), now optionally reporting other cancers too."}]},{"item":"PATHFINDER 2 study completion (primary completion listed as 2026-02-11)","expected":"2028-04-30","source":"https://clinicaltrials.gov/study/NCT05155605","refs":[{"id":"pathfinder-2","kind":"trial","name":"PATHFINDER 2","route":"/trials/pathfinder-2/","status":"active","tldr":"PATHFINDER 2 is the US real-world study of the Galleri test that forms the core of its FDA submission."},{"id":"galleri","kind":"drug","name":"Galleri","route":"/drugs/galleri/","status":"phase-3","tldr":"A blood test screening for more than 50 cancers at once, before the FDA in September 2026."}]},{"item":"Vanguard study primary completion: the NCI's randomised feasibility trial of multi-cancer detection tests in 24,000 people","expected":"2029-01-31","source":"https://clinicaltrials.gov/study/NCT06995898","refs":[{"id":"vanguard-study","kind":"trial","name":"Vanguard Study (NCI Cancer Screening Research Network)","route":"/trials/vanguard-study/","status":"recruiting","tldr":"The US government's first randomised study of multi-cancer blood tests: 24,000 people are being assigned to a blood test or usual care to work out how a much larger trial should be run."},{"id":"nci","kind":"institution","name":"National Cancer Institute (NIH)","route":"/institutions/nci/","tldr":"The NCI is the US government's cancer research agency, spending ~$7B a year and running the Cancer Centers Program, TCGA, and Rosenberg's cell therapy lab."}]},{"item":"CIRCULATE-US primary completion: ctDNA-guided escalation and de-escalation of adjuvant chemotherapy in stage III colon cancer","expected":"2029-03-10","source":"https://clinicaltrials.gov/study/NCT05174169","refs":[{"id":"circulate-us","kind":"trial","name":"CIRCULATE-US","route":"/trials/circulate-us/","status":"recruiting","tldr":"The US national trial that uses a blood test for leftover tumour DNA to decide who gets less chemotherapy and who gets more after stage III colon cancer surgery, with both questions randomised."},{"id":"signatera","kind":"drug","name":"Signatera","route":"/drugs/signatera/","status":"established","tldr":"Signatera is Natera's tumour-informed blood test that tracks 16 mutations from each patient's own tumour to detect residual or returning cancer after surgery. Medicare covers it in colorectal, breast, bladder, lung and ovarian cancer and for immunotherapy monitoring, and in 2026 it selected the bladder cancer patients for the first approval based on circulating tumour DNA."}]},{"item":"TRACC primary completion: 1,000 people with early colorectal cancer followed by ctDNA","expected":"2029-07-31","source":"https://clinicaltrials.gov/study/NCT04050345","refs":[{"id":"tracc","kind":"trial","name":"TRACC","route":"/trials/tracc/","status":"recruiting","tldr":"A UK study following 1,000 people after bowel cancer surgery with repeated blood tests for tumour DNA, to see how well a positive predicts the cancer coming back and whether the result can guide chemotherapy."}]},{"item":"VEGA (CIRCULATE-Japan): non-inferiority of no chemotherapy in ctDNA-negative colon cancer; no readout date in the sources read","source":"https://europepmc.org/article/MED/33931919","refs":[{"id":"circulate-japan","kind":"trial","name":"CIRCULATE-Japan (GALAXY / VEGA / ALTAIR)","route":"/trials/circulate-japan/","status":"active","tldr":"Japan's national programme tests whether a blood test after surgery should decide who gets chemotherapy, and whether treating a positive test early helps."}]},{"item":"BESPOKE CRC: registry status not updated since a listed completion of September 2025; watch for the primary publication","expected":"2025-09","source":"https://clinicaltrials.gov/study/NCT04264702","refs":[{"id":"bespoke-crc","kind":"trial","name":"BESPOKE CRC","route":"/trials/bespoke-crc/","status":"active","tldr":"Natera's US study in which 1,788 people with bowel cancer had Signatera blood tests after surgery and their doctors could act on the result; it records what changed and what happened, but does not randomise anyone."},{"id":"signatera","kind":"drug","name":"Signatera","route":"/drugs/signatera/","status":"established","tldr":"Signatera is Natera's tumour-informed blood test that tracks 16 mutations from each patient's own tumour to detect residual or returning cancer after surgery. Medicare covers it in colorectal, breast, bladder, lung and ovarian cancer and for immunotherapy monitoring, and in 2026 it selected the bladder cancer patients for the first approval based on circulating tumour DNA."}]}]}